UniProtKB - P07101 (TY3H_HUMAN)
Protein
Tyrosine 3-monooxygenase
Gene
TH
Organism
Homo sapiens (Human)
Status
Functioni
Plays an important role in the physiology of adrenergic neurons (By similarity). Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).By similarity
Catalytic activityi
- (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-dopaEC:1.14.16.2
Cofactori
Activity regulationi
Phosphorylation leads to an increase in the catalytic activity.
: dopamine biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes dopamine from L-tyrosine.Proteins known to be involved in the 2 steps of the subpathway in this organism are:
- Tyrosine 3-monooxygenase (TH)
- Aromatic-L-amino-acid decarboxylase (DDC)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes dopamine from L-tyrosine, the pathway dopamine biosynthesis and in Catecholamine biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 361 | IronBy similarity | 1 | |
Metal bindingi | 366 | IronBy similarity | 1 | |
Metal bindingi | 406 | IronBy similarity | 1 |
GO - Molecular functioni
- amino acid binding Source: Ensembl
- dopamine binding Source: Ensembl
- enzyme binding Source: ParkinsonsUK-UCL
- ferric iron binding Source: Ensembl
- ferrous iron binding Source: Ensembl
- identical protein binding Source: IntAct
- oxygen binding Source: Ensembl
- protein domain specific binding Source: Ensembl
- tetrahydrobiopterin binding Source: Ensembl
- tyrosine 3-monooxygenase activity Source: UniProtKB
GO - Biological processi
- aminergic neurotransmitter loading into synaptic vesicle Source: Ensembl
- anatomical structure morphogenesis Source: ProtInc
- animal organ morphogenesis Source: BHF-UCL
- catecholamine biosynthetic process Source: Reactome
- cellular response to alkaloid Source: Ensembl
- cellular response to drug Source: Ensembl
- cellular response to glucose stimulus Source: Ensembl
- cellular response to growth factor stimulus Source: Ensembl
- cellular response to manganese ion Source: Ensembl
- cellular response to nicotine Source: Ensembl
- cerebral cortex development Source: Ensembl
- circadian sleep/wake cycle Source: Ensembl
- dopamine biosynthetic process Source: BHF-UCL
- dopamine biosynthetic process from tyrosine Source: GO_Central
- eating behavior Source: Ensembl
- embryonic camera-type eye morphogenesis Source: BHF-UCL
- epinephrine biosynthetic process Source: BHF-UCL
- eye photoreceptor cell development Source: BHF-UCL
- fatty acid metabolic process Source: Ensembl
- glycoside metabolic process Source: Ensembl
- heart development Source: BHF-UCL
- heart morphogenesis Source: BHF-UCL
- hyaloid vascular plexus regression Source: UniProtKB
- isoquinoline alkaloid metabolic process Source: Ensembl
- learning Source: BHF-UCL
- locomotory behavior Source: BHF-UCL
- mating behavior Source: Ensembl
- memory Source: BHF-UCL
- multicellular organism aging Source: Ensembl
- neurotransmitter biosynthetic process Source: UniProtKB-KW
- norepinephrine biosynthetic process Source: BHF-UCL
- phthalate metabolic process Source: Ensembl
- phytoalexin metabolic process Source: Ensembl
- pigmentation Source: BHF-UCL
- regulation of heart contraction Source: BHF-UCL
- response to activity Source: Ensembl
- response to amphetamine Source: Ensembl
- response to corticosterone Source: Ensembl
- response to electrical stimulus Source: Ensembl
- response to estradiol Source: Ensembl
- response to ethanol Source: BHF-UCL
- response to ether Source: Ensembl
- response to herbicide Source: Ensembl
- response to hypoxia Source: BHF-UCL
- response to immobilization stress Source: Ensembl
- response to isolation stress Source: Ensembl
- response to light stimulus Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- response to nutrient levels Source: Ensembl
- response to peptide hormone Source: Ensembl
- response to pyrethroid Source: Ensembl
- response to salt stress Source: Ensembl
- response to water deprivation Source: Ensembl
- response to zinc ion Source: Ensembl
- sensory perception of sound Source: Ensembl
- social behavior Source: Ensembl
- sphingolipid metabolic process Source: Ensembl
- synaptic transmission, dopaminergic Source: BHF-UCL
- terpene metabolic process Source: Ensembl
- visual perception Source: BHF-UCL
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Catecholamine biosynthesis, Neurotransmitter biosynthesis |
Ligand | Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 1.14.16.2, 2681 |
PathwayCommonsi | P07101 |
Reactomei | R-HSA-209905, Catecholamine biosynthesis |
SIGNORi | P07101 |
UniPathwayi | UPA00747;UER00733 |
Names & Taxonomyi
Protein namesi | Recommended name: Tyrosine 3-monooxygenase (EC:1.14.16.2)Alternative name(s): Tyrosine 3-hydroxylase Short name: TH |
Gene namesi | Name:TH Synonyms:TYH |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000180176.14 |
HGNCi | HGNC:11782, TH |
MIMi | 191290, gene |
neXtProti | NX_P07101 |
Subcellular locationi
Other locations
- perinuclear region By similarity
Cytosol
- cytosol Source: Reactome
Endoplasmic reticulum
- smooth endoplasmic reticulum Source: BHF-UCL
Mitochondrion
- mitochondrion Source: Ensembl
Nucleus
- nucleus Source: BHF-UCL
Plasma Membrane
- cytoplasmic side of plasma membrane Source: BHF-UCL
Other locations
- axon Source: GO_Central
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle Source: BHF-UCL
- dendrite Source: Ensembl
- melanosome membrane Source: BHF-UCL
- neuron projection Source: BHF-UCL
- perikaryon Source: BHF-UCL
- perinuclear region of cytoplasm Source: UniProtKB
- synaptic vesicle Source: Ensembl
- terminal bouton Source: Ensembl
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Segawa syndrome autosomal recessive (ARSEGS)23 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of DOPA-responsive dystonia presenting in infancy or early childhood. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Some cases present with parkinsonian symptoms in infancy. Unlike all other forms of dystonia, it is an eminently treatable condition, due to a favorable response to L-DOPA.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072863 | 207 | C → Y in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072864 | 227 | D → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_014026 | 233 | R → H in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 4 PublicationsCorresponds to variant dbSNP:rs80338892Ensembl. | 1 | |
Natural variantiVAR_014027 | 236 | L → P in ARSEGS; severe parkinsonian symptoms in early infancy; strongly reduced stability and catalytic activity; rare mutation. 3 PublicationsCorresponds to variant dbSNP:rs121917763Ensembl. | 1 | |
Natural variantiVAR_072865 | 241 | A → T in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1260455415Ensembl. | 1 | |
Natural variantiVAR_072866 | 246 | H → Y in ARSEGS; loss of about 40% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072867 | 247 | G → S in ARSEGS; loss of about 50% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 PublicationsCorresponds to variant dbSNP:rs762304556Ensembl. | 1 | |
Natural variantiVAR_071715 | 251 | P → L in ARSEGS. 1 Publication | 1 | |
Natural variantiVAR_072868 | 259 | E → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_014028 | 276 | T → P in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs28934581Ensembl. | 1 | |
Natural variantiVAR_071716 | 279 | C → F in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs1273610334Ensembl. | 1 | |
Natural variantiVAR_072869 | 294 | G → R in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs755536257Ensembl. | 1 | |
Natural variantiVAR_071717 | 296 | R → Q in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs199961079Ensembl. | 1 | |
Natural variantiVAR_072870 | 301 | P → A in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072871 | 309 | F → S in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_014029 | 314 | T → M in ARSEGS; parkinsonian symptoms in infancy; loss of about 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs121917764Ensembl. | 1 | |
Natural variantiVAR_071718 | 315 | G → S in ARSEGS. 2 PublicationsCorresponds to variant dbSNP:rs1288483479Ensembl. | 1 | |
Natural variantiVAR_072872 | 319 | R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072873 | 328 | R → W in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1428589694Ensembl. | 1 | |
Natural variantiVAR_014030 | 337 | R → H in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs28934580Ensembl. | 1 | |
Natural variantiVAR_072874 | 359 | C → F in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs121917765Ensembl. | 1 | |
Natural variantiVAR_072875 | 375 | F → L in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 PublicationsCorresponds to variant dbSNP:rs763198914Ensembl. | 1 | |
Natural variantiVAR_072876 | 376 | A → V in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_071719 | 382 | I → T in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs1554922725Ensembl. | 1 | |
Natural variantiVAR_072877 | 385 | A → V in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs763039181Ensembl. | 1 | |
Natural variantiVAR_072878 | 387 | L → M in ARSEGS; no effect on tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072879 | 394 | I → T in ARSEGS; complete loss of tyrosine hydroxylase activity. 3 Publications | 1 | |
Natural variantiVAR_072880 | 399 | T → M in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1057520384EnsemblClinVar. | 1 | |
Natural variantiVAR_072881 | 408 | G → R in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs745551241Ensembl. | 1 | |
Natural variantiVAR_014031 | 412 | Q → K in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; reduced affinity for L-tyrosine. 3 PublicationsCorresponds to variant dbSNP:rs121917762Ensembl. | 1 | |
Natural variantiVAR_072882 | 414 | G → R in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 3 PublicationsCorresponds to variant dbSNP:rs370962049Ensembl. | 1 | |
Natural variantiVAR_071720 | 428 | G → R in ARSEGS; phenotype with prominent levodopa-responsive myoconus-dystonia (M-D). 2 PublicationsCorresponds to variant dbSNP:rs1264884607Ensembl. | 1 | |
Natural variantiVAR_072883 | 441 | R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs367874223Ensembl. | 1 | |
Natural variantiVAR_072884 | 467 | S → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072885 | 492 | P → L in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs767635052Ensembl. | 1 | |
Natural variantiVAR_014032 | 494 | T → M in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs45471299Ensembl. | 1 | |
Natural variantiVAR_072886 | 498 | D → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 4 PublicationsCorresponds to variant dbSNP:rs771351747Ensembl. | 1 | |
Natural variantiVAR_072887 | 510 | L → Q in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 |
May play a role in the pathogenesis of Parkinson disease (PD). A genome-wide copy number variation analysis has identified a 34 kilobase deletion over the TH gene in a PD patient but not in any controls.1 Publication
Keywords - Diseasei
Disease mutation, Dystonia, Parkinson disease, ParkinsonismOrganism-specific databases
DisGeNETi | 7054 |
GeneReviewsi | TH |
MalaCardsi | TH |
MIMi | 605407, phenotype |
OpenTargetsi | ENSG00000180176 |
Orphaneti | 101150, Autosomal recessive dopa-responsive dystonia |
PharmGKBi | PA351 |
Miscellaneous databases
Pharosi | P07101, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1969 |
DrugBanki | DB03552, 3-Tyrosine DB04400, L-erythro-7,8-dihydrobiopterin DB00765, Metyrosine DB00120, Phenylalanine DB00360, Sapropterin DB00135, Tyrosine |
DrugCentrali | P07101 |
Polymorphism and mutation databases
BioMutai | TH |
DMDMi | 239938945 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000205561 | 1 – 528 | Tyrosine 3-monooxygenaseAdd BLAST | 528 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 19 | Phosphoserine; by CaMK21 Publication | 1 | |
Modified residuei | 62 | PhosphoserineBy similarity | 1 | |
Modified residuei | 71 | Phosphoserine; by CaMK2 and PKA1 Publication | 1 | |
Modified residuei | 502 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | P07101 |
MassIVEi | P07101 |
PaxDbi | P07101 |
PeptideAtlasi | P07101 |
PRIDEi | P07101 |
ProteomicsDBi | 51950 [P07101-1] 51951 [P07101-2] 51952 [P07101-3] 51953 [P07101-4] 58784 |
PTM databases
iPTMneti | P07101 |
PhosphoSitePlusi | P07101 |
Expressioni
Tissue specificityi
Mainly expressed in the brain and adrenal glands.
Gene expression databases
Bgeei | ENSG00000180176, Expressed in substantia nigra and 104 other tissues |
ExpressionAtlasi | P07101, baseline and differential |
Genevisiblei | P07101, HS |
Organism-specific databases
HPAi | ENSG00000180176, Group enriched (adrenal gland, brain) |
Interactioni
Binary interactionsi
Hide detailsTH - isoform 2 [P07101-3]
GO - Molecular functioni
- enzyme binding Source: ParkinsonsUK-UCL
- identical protein binding Source: IntAct
- protein domain specific binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 112912, 28 interactors |
ELMi | P07101 |
IntActi | P07101, 22 interactors |
MINTi | P07101 |
STRINGi | 9606.ENSP00000370571 |
Chemistry databases
BindingDBi | P07101 |
Miscellaneous databases
RNActi | P07101, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SASBDBi | P07101 |
SMRi | P07101 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 85 – 90 | Poly-Ala | 6 |
Sequence similaritiesi
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.Curated
Phylogenomic databases
eggNOGi | KOG3820, Eukaryota |
GeneTreei | ENSGT00950000182885 |
HOGENOMi | CLU_023198_3_0_1 |
InParanoidi | P07101 |
OMAi | SVKAPWF |
PhylomeDBi | P07101 |
TreeFami | TF313327 |
Family and domain databases
CDDi | cd03345, eu_TyrOH, 1 hit |
Gene3Di | 1.10.800.10, 1 hit |
InterProi | View protein in InterPro IPR001273, ArAA_hydroxylase IPR018301, ArAA_hydroxylase_Fe/CU_BS IPR036951, ArAA_hydroxylase_sf IPR036329, Aro-AA_hydroxylase_C_sf IPR019774, Aromatic-AA_hydroxylase_C IPR041903, Eu_TyrOH_cat IPR005962, Tyr_3_mOase IPR019773, Tyrosine_3-monooxygenase-like IPR021164, Tyrosine_hydroxylase_CS |
PANTHERi | PTHR11473, PTHR11473, 1 hit |
Pfami | View protein in Pfam PF00351, Biopterin_H, 1 hit PF12549, TOH_N, 3 hits |
PIRSFi | PIRSF000336, TH, 1 hit |
PRINTSi | PR00372, FYWHYDRXLASE |
SUPFAMi | SSF56534, SSF56534, 1 hit |
TIGRFAMsi | TIGR01269, Tyr_3_monoox, 1 hit |
PROSITEi | View protein in PROSITE PS00367, BH4_AAA_HYDROXYL_1, 1 hit PS51410, BH4_AAA_HYDROXYL_2, 1 hit |
s (6+)i Sequence
Sequence statusi: Complete.
This entry describes 6 produced by isoformsialternative splicing. AlignAdd to basketNote: TH transcripts lacking exons 8 and 9 present concomitant splicing in exons 1b and 2.
This entry has 6 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 3 (identifier: P07101-1) [UniParc]FASTAAdd to basket
Also known as: TH type 4
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPTPDATTPQ AKGFRRAVSE LDAKQAEAIM VRGQGAPGPS LTGSPWPGTA
60 70 80 90 100
APAASYTPTP RSPRFIGRRQ SLIEDARKER EAAVAAAAAA VPSEPGDPLE
110 120 130 140 150
AVAFEEKEGK AVLNLLFSPR ATKPSALSRA VKVFETFEAK IHHLETRPAQ
160 170 180 190 200
RPRAGGPHLE YFVRLEVRRG DLAALLSGVR QVSEDVRSPA GPKVPWFPRK
210 220 230 240 250
VSELDKCHHL VTKFDPDLDL DHPGFSDQVY RQRRKLIAEI AFQYRHGDPI
260 270 280 290 300
PRVEYTAEEI ATWKEVYTTL KGLYATHACG EHLEAFALLE RFSGYREDNI
310 320 330 340 350
PQLEDVSRFL KERTGFQLRP VAGLLSARDF LASLAFRVFQ CTQYIRHASS
360 370 380 390 400
PMHSPEPDCC HELLGHVPML ADRTFAQFSQ DIGLASLGAS DEEIEKLSTL
410 420 430 440 450
YWFTVEFGLC KQNGEVKAYG AGLLSSYGEL LHCLSEEPEI RAFDPEAAAV
460 470 480 490 500
QPYQDQTYQS VYFVSESFSD AKDKLRSYAS RIQRPFSVKF DPYTLAIDVL
510 520
DSPQAVRRSL EGVQDELDTL AHALSAIG
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0Y670 | H0Y670_HUMAN | Tyrosine 3-monooxygenase | TH | 45 | Annotation score: | ||
H0Y677 | H0Y677_HUMAN | Tyrosine 3-monooxygenase | TH | 116 | Annotation score: | ||
E7EQI0 | E7EQI0_HUMAN | Tyrosine 3-monooxygenase | TH | 48 | Annotation score: | ||
F8W8M5 | F8W8M5_HUMAN | Tyrosine 3-monooxygenase | TH | 44 | Annotation score: |
Sequence cautioni
The sequence AAA61173 differs from that shown. Reason: Erroneous gene model prediction.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 373 | R → H in AAI43615 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 401 | Y → S in AAA61179 (PubMed:2887169).Curated | 1 | |
Sequence conflicti | 401 | Y → S in CAA28908 (PubMed:2882428).Curated | 1 | |
Sequence conflicti | 401 | Y → S in CAA68472 (PubMed:2888085).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072862 | 19 | S → C Found in a patient with ARSEGS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs766704202Ensembl. | 1 | |
Natural variantiVAR_014025 | 112 | V → M Common polymorphism. 5 PublicationsCorresponds to variant dbSNP:rs6356Ensembl. | 1 | |
Natural variantiVAR_072863 | 207 | C → Y in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072864 | 227 | D → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_014026 | 233 | R → H in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 4 PublicationsCorresponds to variant dbSNP:rs80338892Ensembl. | 1 | |
Natural variantiVAR_014027 | 236 | L → P in ARSEGS; severe parkinsonian symptoms in early infancy; strongly reduced stability and catalytic activity; rare mutation. 3 PublicationsCorresponds to variant dbSNP:rs121917763Ensembl. | 1 | |
Natural variantiVAR_072865 | 241 | A → T in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1260455415Ensembl. | 1 | |
Natural variantiVAR_072866 | 246 | H → Y in ARSEGS; loss of about 40% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072867 | 247 | G → S in ARSEGS; loss of about 50% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 PublicationsCorresponds to variant dbSNP:rs762304556Ensembl. | 1 | |
Natural variantiVAR_071715 | 251 | P → L in ARSEGS. 1 Publication | 1 | |
Natural variantiVAR_072868 | 259 | E → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_014028 | 276 | T → P in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs28934581Ensembl. | 1 | |
Natural variantiVAR_071716 | 279 | C → F in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs1273610334Ensembl. | 1 | |
Natural variantiVAR_072869 | 294 | G → R in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs755536257Ensembl. | 1 | |
Natural variantiVAR_071717 | 296 | R → Q in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs199961079Ensembl. | 1 | |
Natural variantiVAR_072870 | 301 | P → A in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072871 | 309 | F → S in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_014029 | 314 | T → M in ARSEGS; parkinsonian symptoms in infancy; loss of about 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs121917764Ensembl. | 1 | |
Natural variantiVAR_071718 | 315 | G → S in ARSEGS. 2 PublicationsCorresponds to variant dbSNP:rs1288483479Ensembl. | 1 | |
Natural variantiVAR_072872 | 319 | R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072873 | 328 | R → W in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1428589694Ensembl. | 1 | |
Natural variantiVAR_014030 | 337 | R → H in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs28934580Ensembl. | 1 | |
Natural variantiVAR_072874 | 359 | C → F in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs121917765Ensembl. | 1 | |
Natural variantiVAR_072875 | 375 | F → L in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 PublicationsCorresponds to variant dbSNP:rs763198914Ensembl. | 1 | |
Natural variantiVAR_072876 | 376 | A → V in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_071719 | 382 | I → T in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs1554922725Ensembl. | 1 | |
Natural variantiVAR_072877 | 385 | A → V in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs763039181Ensembl. | 1 | |
Natural variantiVAR_072878 | 387 | L → M in ARSEGS; no effect on tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072879 | 394 | I → T in ARSEGS; complete loss of tyrosine hydroxylase activity. 3 Publications | 1 | |
Natural variantiVAR_072880 | 399 | T → M in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1057520384EnsemblClinVar. | 1 | |
Natural variantiVAR_072881 | 408 | G → R in ARSEGS. 1 PublicationCorresponds to variant dbSNP:rs745551241Ensembl. | 1 | |
Natural variantiVAR_014031 | 412 | Q → K in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; reduced affinity for L-tyrosine. 3 PublicationsCorresponds to variant dbSNP:rs121917762Ensembl. | 1 | |
Natural variantiVAR_072882 | 414 | G → R in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 3 PublicationsCorresponds to variant dbSNP:rs370962049Ensembl. | 1 | |
Natural variantiVAR_071720 | 428 | G → R in ARSEGS; phenotype with prominent levodopa-responsive myoconus-dystonia (M-D). 2 PublicationsCorresponds to variant dbSNP:rs1264884607Ensembl. | 1 | |
Natural variantiVAR_072883 | 441 | R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs367874223Ensembl. | 1 | |
Natural variantiVAR_072884 | 467 | S → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications | 1 | |
Natural variantiVAR_072885 | 492 | P → L in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs767635052Ensembl. | 1 | |
Natural variantiVAR_014032 | 494 | T → M in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs45471299Ensembl. | 1 | |
Natural variantiVAR_072886 | 498 | D → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 4 PublicationsCorresponds to variant dbSNP:rs771351747Ensembl. | 1 | |
Natural variantiVAR_014033 | 499 | V → M1 PublicationCorresponds to variant dbSNP:rs1800033Ensembl. | 1 | |
Natural variantiVAR_072887 | 510 | L → Q in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_000544 | 31 – 61 | Missing in isoform 2 and isoform 6. 3 PublicationsAdd BLAST | 31 | |
Alternative sequenceiVSP_000543 | 31 – 34 | Missing in isoform 1. 1 Publication | 4 | |
Alternative sequenceiVSP_000541 | 35 – 61 | Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST | 27 | |
Alternative sequenceiVSP_054338 | 264 – 357 | Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST | 94 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M17589 mRNA Translation: AAA61179.1 X05290 mRNA Translation: CAA28908.1 Y00414 mRNA Translation: CAA68472.1 DQ677336 mRNA Translation: ABG73364.1 DQ677337 mRNA Translation: ABG73365.1 AC132217 Genomic DNA No translation available. M24791, M24787, M24789 Genomic DNA Translation: AAA61173.1 Sequence problems. CH471158 Genomic DNA Translation: EAX02493.1 BC104967 mRNA Translation: AAI04968.1 BC143611 mRNA Translation: AAI43612.1 BC143614 mRNA Translation: AAI43615.1 M24791, M24787 Genomic DNA Translation: AAA61170.1 M20911 mRNA Translation: AAA61167.1 |
CCDSi | CCDS31338.1 [P07101-2] CCDS7730.1 [P07101-3] CCDS7731.1 [P07101-1] |
PIRi | A30002, WHHUY4 |
RefSeqi | NP_000351.2, NM_000360.3 [P07101-3] NP_954986.2, NM_199292.2 [P07101-1] NP_954987.2, NM_199293.2 [P07101-2] XP_011518637.1, XM_011520335.2 [P07101-4] |
Genome annotation databases
Ensembli | ENST00000333684; ENSP00000328814; ENSG00000180176 [P07101-6] ENST00000352909; ENSP00000325951; ENSG00000180176 [P07101-3] ENST00000381175; ENSP00000370567; ENSG00000180176 [P07101-2] ENST00000381178; ENSP00000370571; ENSG00000180176 [P07101-1] |
GeneIDi | 7054 |
KEGGi | hsa:7054 |
UCSCi | uc001lvp.3, human [P07101-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Tyrosine hydroxylase entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M17589 mRNA Translation: AAA61179.1 X05290 mRNA Translation: CAA28908.1 Y00414 mRNA Translation: CAA68472.1 DQ677336 mRNA Translation: ABG73364.1 DQ677337 mRNA Translation: ABG73365.1 AC132217 Genomic DNA No translation available. M24791, M24787, M24789 Genomic DNA Translation: AAA61173.1 Sequence problems. CH471158 Genomic DNA Translation: EAX02493.1 BC104967 mRNA Translation: AAI04968.1 BC143611 mRNA Translation: AAI43612.1 BC143614 mRNA Translation: AAI43615.1 M24791, M24787 Genomic DNA Translation: AAA61170.1 M20911 mRNA Translation: AAA61167.1 |
CCDSi | CCDS31338.1 [P07101-2] CCDS7730.1 [P07101-3] CCDS7731.1 [P07101-1] |
PIRi | A30002, WHHUY4 |
RefSeqi | NP_000351.2, NM_000360.3 [P07101-3] NP_954986.2, NM_199292.2 [P07101-1] NP_954987.2, NM_199293.2 [P07101-2] XP_011518637.1, XM_011520335.2 [P07101-4] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2XSN | X-ray | 2.68 | A/B/C/D | 193-528 | [»] | |
4J6S | X-ray | 3.08 | E/F/G/H | 1-74 | [»] | |
SASBDBi | P07101 | |||||
SMRi | P07101 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112912, 28 interactors |
ELMi | P07101 |
IntActi | P07101, 22 interactors |
MINTi | P07101 |
STRINGi | 9606.ENSP00000370571 |
Chemistry databases
BindingDBi | P07101 |
ChEMBLi | CHEMBL1969 |
DrugBanki | DB03552, 3-Tyrosine DB04400, L-erythro-7,8-dihydrobiopterin DB00765, Metyrosine DB00120, Phenylalanine DB00360, Sapropterin DB00135, Tyrosine |
DrugCentrali | P07101 |
PTM databases
iPTMneti | P07101 |
PhosphoSitePlusi | P07101 |
Polymorphism and mutation databases
BioMutai | TH |
DMDMi | 239938945 |
Proteomic databases
jPOSTi | P07101 |
MassIVEi | P07101 |
PaxDbi | P07101 |
PeptideAtlasi | P07101 |
PRIDEi | P07101 |
ProteomicsDBi | 51950 [P07101-1] 51951 [P07101-2] 51952 [P07101-3] 51953 [P07101-4] 58784 |
Protocols and materials databases
Antibodypediai | 3748, 1604 antibodies |
Genome annotation databases
Ensembli | ENST00000333684; ENSP00000328814; ENSG00000180176 [P07101-6] ENST00000352909; ENSP00000325951; ENSG00000180176 [P07101-3] ENST00000381175; ENSP00000370567; ENSG00000180176 [P07101-2] ENST00000381178; ENSP00000370571; ENSG00000180176 [P07101-1] |
GeneIDi | 7054 |
KEGGi | hsa:7054 |
UCSCi | uc001lvp.3, human [P07101-1] |
Organism-specific databases
CTDi | 7054 |
DisGeNETi | 7054 |
EuPathDBi | HostDB:ENSG00000180176.14 |
GeneCardsi | TH |
GeneReviewsi | TH |
HGNCi | HGNC:11782, TH |
HPAi | ENSG00000180176, Group enriched (adrenal gland, brain) |
MalaCardsi | TH |
MIMi | 191290, gene 605407, phenotype |
neXtProti | NX_P07101 |
OpenTargetsi | ENSG00000180176 |
Orphaneti | 101150, Autosomal recessive dopa-responsive dystonia |
PharmGKBi | PA351 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3820, Eukaryota |
GeneTreei | ENSGT00950000182885 |
HOGENOMi | CLU_023198_3_0_1 |
InParanoidi | P07101 |
OMAi | SVKAPWF |
PhylomeDBi | P07101 |
TreeFami | TF313327 |
Enzyme and pathway databases
UniPathwayi | UPA00747;UER00733 |
BRENDAi | 1.14.16.2, 2681 |
PathwayCommonsi | P07101 |
Reactomei | R-HSA-209905, Catecholamine biosynthesis |
SIGNORi | P07101 |
Miscellaneous databases
BioGRID-ORCSi | 7054, 6 hits in 849 CRISPR screens |
GeneWikii | Tyrosine_hydroxylase |
GenomeRNAii | 7054 |
Pharosi | P07101, Tclin |
PROi | PR:P07101 |
RNActi | P07101, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000180176, Expressed in substantia nigra and 104 other tissues |
ExpressionAtlasi | P07101, baseline and differential |
Genevisiblei | P07101, HS |
Family and domain databases
CDDi | cd03345, eu_TyrOH, 1 hit |
Gene3Di | 1.10.800.10, 1 hit |
InterProi | View protein in InterPro IPR001273, ArAA_hydroxylase IPR018301, ArAA_hydroxylase_Fe/CU_BS IPR036951, ArAA_hydroxylase_sf IPR036329, Aro-AA_hydroxylase_C_sf IPR019774, Aromatic-AA_hydroxylase_C IPR041903, Eu_TyrOH_cat IPR005962, Tyr_3_mOase IPR019773, Tyrosine_3-monooxygenase-like IPR021164, Tyrosine_hydroxylase_CS |
PANTHERi | PTHR11473, PTHR11473, 1 hit |
Pfami | View protein in Pfam PF00351, Biopterin_H, 1 hit PF12549, TOH_N, 3 hits |
PIRSFi | PIRSF000336, TH, 1 hit |
PRINTSi | PR00372, FYWHYDRXLASE |
SUPFAMi | SSF56534, SSF56534, 1 hit |
TIGRFAMsi | TIGR01269, Tyr_3_monoox, 1 hit |
PROSITEi | View protein in PROSITE PS00367, BH4_AAA_HYDROXYL_1, 1 hit PS51410, BH4_AAA_HYDROXYL_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TY3H_HUMAN | |
Accessioni | P07101Primary (citable) accession number: P07101 Secondary accession number(s): B7ZL70 Q2M3B4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1988 |
Last sequence update: | June 16, 2009 | |
Last modified: | December 2, 2020 | |
This is version 224 of the entry and version 5 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations